Outcomes of alternative (second-line) antiandrogen therapy in 112 patients with relapsing prostate cancer after first-line hormonal therapy were analyzed. A good response (prostate-specific antigen [PSA] decrease 50%) and a partial response (PSA decrease of 0–50%) by switching from bicalutamide (BCL) to flutamide (FLT) and from FLT to BCL were achieved in 35.4% (28/79) and 30.4% (24/79), and in 45.0% (9/20) and 20.0% (4/20) of cases, respectively. A good response and a partial response with the change from chlormadinone acetate (CMA) to a non-steroidal antiandrogen (FLT or BCL)and from a non-steroidal antiandrogen to CMA were obtained in 25.0% (2/8) and 37.5% (3/8), and in 20.0% (1/5) and 0% (0/5)of cases, respectively. In multivariate analyses, a second-line good response was significantly predictive of cause-specific survival from first therapy relapse to cancer death in all patients. Patients (52/112, 46.4%) with 30% decrease in PSA levels were associated with significantly better cause-specific survival as measured from the start of first-line treatment and first-line relapse.